小柯机器人

近日，大连医科大学杨庆凯等研究人员合作发现，精胺通过稳定DNA与DNA传感器cGAS的结合来增强抗病毒和抗癌反应。这一研究成果于2023年1月31日在线发表在国际学术期刊《免疫》上。

研究人员表示，自我-非自我辨别对于免疫系统在对病原体产生反应的同时保持对宿主和无害共生生物的耐受性是至关重要的。

研究人员报道了不加区分的DNA传感器，如循环GMP-AMP合成酶（cGAS），是如何进行这种自我-非自我区分的。对一个小分子文库的筛选显示，精胺（一种与病毒DNA相关的著名DNA凝聚分子）显著提高了cGAS的激活。在机制上，精胺凝聚DNA来增强和稳定cGAS-DNA结合，从而优化cGAS和下游抗病毒信号。精胺促进病毒DNA凝聚，但不促进宿主核小体DNA凝聚。通过在精胺缺乏的细胞中繁殖病毒，删除病毒DNA相关的精胺降低了cGAS的激活。精胺耗竭随后减弱了cGAS介导的抗病毒和抗癌免疫。总的来说，这些结果揭示了一种致病的DNA相关分子模式，其促进了非自我识别，并将代谢和病原体识别联系起来。

附：英文原文

Title: Spermine enhances antiviral and anticancer responses by stabilizing DNA binding with the DNA sensor cGAS

Author: Lina Wang, Siru Li, Kai Wang, Na Wang, Qiaoling Liu, Zhen Sun, Li Wang, Lulu Wang, Quentin Liu, Chengli Song, Qingkai Yang

Issue&Volume: 2023-01-31

Abstract: Self-nonself discrimination is vital for the immune system to mount responses against pathogens while maintaining tolerance toward the host and innocuous commensals during homeostasis. Here, we investigated how indiscriminate DNA sensors, such as cyclic GMP-AMP synthase (cGAS), make this self-nonself distinction. Screening of a small-molecule library revealed that spermine, a well-known DNA condenser associated with viral DNA, markedly elevates cGAS activation. Mechanistically, spermine condenses DNA to enhance and stabilize cGAS-DNA binding, optimizing cGAS and downstream antiviral signaling. Spermine promotes condensation of viral, but not host nucleosome, DNA. Deletion of viral DNA-associated spermine, by propagating virus in spermine-deficient cells, reduced cGAS activation. Spermine depletion subsequently attenuated cGAS-mediated antiviral and anticancer immunity. Collectively, our results reveal a pathogenic DNA-associated molecular pattern that facilitates nonself recognition, linking metabolism and pathogen recognition.

DOI: 10.1016/j.immuni.2023.01.001

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00011-0

Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：43.474
官方网址：https://www.cell.com/immunity/home
投稿链接：https://www.editorialmanager.com/immunity/default.aspx